Friday, November 20, 2015

MCR-1: The Return Of The Plasmids

Although it may sound like a likely title for the next Star Wars installment, Plasmids are tiny snippets of DNA that can be easily transferred between different types of bacteria, and as we’ve seen with NDM-1 and other variants, they can convey antibiotic resistance to their new hosts.

The NDM-1 (New Delhi metallo-ß-lactamase-1) enzyme – which has received considerable attention these past five years – conveys resistance to the Carbapenem class of antibiotics, which are often used as the drug of last resort for treating difficult bacterial infections, including Escherichia coli (E. coli) and Klebsiella pneumoniae.

It may help if you think of plasmids as vehicles that can travel between different types of bacteria, and the resistance genes (like NDM-1) as one of its passengers.

Since it requires physical contact between two different types of bacteria for plasmids to transfer, man-made environments where many types of bacteria are thrown together - such as sewage treatment plants and contaminated water supplies - are of great interest to microbiologists studying plasmids.

Resistant bacteria were found in 4 per cent of the water supplies and 30 per cent of the seepage sites. The researchers identified 11 new species of bacteria carrying the NDM-1 gene, including strains which causecholera and dysentery.

Since then we’ve seen a steady stream of reports of NDM-1 (and variants, like NDM-2, NDM-4, NDM-5, etc) turn up around the globe.

This week, just in time for our annual Global Antibiotic Awareness week, Professor Walsh is back with another group of researchers, unveiling the discovery of a new resistance gene discovered in China that breaches the last ditch class of antibiotics; polymyxins.

Background

Until now, polymyxin resistance has involved chromosomal mutations but has never been reported via horizontal gene transfer. During a routine surveillance project on antimicrobial resistance in commensal Escherichia coli from food animals in China, a major increase of colistin resistance was observed. When an E coli strain, SHP45, possessing colistin resistance that could be transferred to another strain, was isolated from a pig, we conducted further analysis of possible plasmid-mediated polymyxin resistance. Herein, we report the emergence of the first plasmid-mediated polymyxin resistance mechanism, MCR-1, in Enterobacteriaceae.

(SNIP)

Findings

Polymyxin resistance was shown to be singularly due to the plasmid-mediated mcr-1 gene. The plasmid carrying mcr-1 was mobilised to an E coli recipient at a frequency of 10−1 to 10−3 cells per recipient cell by conjugation, and maintained in K pneumoniae and Pseudomonas aeruginosa. In an in-vivo model, production of MCR-1 negated the efficacy of colistin. MCR-1 is a member of the phosphoethanolamine transferase enzyme family, with expression in E coli resulting in the addition of phosphoethanolamine to lipid A. We observed mcr-1 carriage in E coli isolates collected from 78 (15%) of 523 samples of raw meat and 166 (21%) of 804 animals during 2011–14, and 16 (1%) of 1322 samples from inpatients with infection.

Interpretation

The emergence of MCR-1 heralds the breach of the last group of antibiotics, polymyxins, by plasmid-mediated resistance. Although currently confined to China, MCR-1 is likely to emulate other global resistance mechanisms such as NDM-1. Our findings emphasise the urgent need for coordinated global action in the fight against pan-drug-resistant Gram-negative bacteria.

Funding

Ministry of Science and Technology of China, National Natural Science Foundation of China.